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Updated: May 23, 2026

Manipulation and Analysis of Cell Cycle-Dependent Processes in Budding Yeast
Published on: September 26, 2025
Cyclin-dependent kinase 8 regulates mitotic commitment in fission yeast
Zsolt Szilagyi1, Gabor Banyai, Marcela Davila Lopez
1Department of Medical Biochemistry and Cell Biology, University of Gothenburg, Gothenburg, Sweden. zsolt.szilagyi@medkem.gu.se
Abstract:
Temporal changes in transcription programs are coupled to control of cell growth and division. We here report that Mediator, a conserved coregulator of eukaryotic transcription, is part of a regulatory pathway that controls mitotic entry in fission yeast. The Mediator subunit cyclin-dependent kinase 8 (Cdk8) phosphorylates the forkhead 2 (Fkh2) protein in a periodic manner that coincides with gene activation during mitosis. Phosphorylation prevents degradation of the Fkh2 transcription factor by the proteasome, thus ensuring cell cycle-dependent variations in Fkh2 levels. Interestingly, Cdk8-dependent phosphorylation of Fkh2 controls mitotic entry, and mitotic entry is delayed by inactivation of the Cdk8 kinase activity or mutations replacing the phosphorylated serine residues of Fkh2. In addition, mutations in Fkh2, which mimic protein phosphorylation, lead to premature mitotic entry. Therefore, Fkh2 regulates not only the onset of mitotic transcription but also the correct timing of mitotic entry via effects on the Wee1 kinase. Our findings thus establish a new pathway linking the Mediator complex to control of mitotic transcription and regulation of mitotic entry in fission yeast.
Insights
The Mediator complex subunit Cdk8 controls cell cycle progression by phosphorylating the Fkh2 transcription factor. This phosphorylation prevents Fkh2 degradation, ensuring proper timing of mitotic entry in fission yeast.
Area of Science:
- Molecular Biology
- Cell Biology
- Genetics
Background:
- Temporal regulation of transcription is crucial for cell growth and division.
- The Mediator complex is a key eukaryotic transcription regulator.
- Control of mitotic entry is essential for accurate cell cycle progression.
Purpose of the Study:
- To investigate the role of the Mediator complex in controlling cell division.
- To elucidate the regulatory pathway involving Mediator subunit Cdk8 and transcription factor Fkh2.
- To understand how transcription factor stability impacts mitotic entry timing.
Main Methods:
- Investigated Mediator subunit Cdk8's role in fission yeast transcription.
- Analyzed Cdk8-mediated phosphorylation of transcription factor Fkh2.
- Assessed the impact of phosphorylation on Fkh2 stability and mitotic entry.
Main Results:
- Mediator subunit Cdk8 periodically phosphorylates Fkh2 during mitosis.
- Phosphorylation by Cdk8 stabilizes Fkh2 against proteasomal degradation.
- Cdk8-Fkh2 interaction is critical for timely mitotic entry and mitotic transcription.
Conclusions:
- A novel pathway links the Mediator complex to mitotic transcription control.
- Cdk8-dependent Fkh2 regulation governs the timing of mitotic entry.
- This pathway ensures cell cycle-dependent gene activation and division.
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